An Automated Device for High Yield Mesenchymal Stem Cell Extraction

项目摘要/摘要 这一二期项目旨在开发一种提取间充质干细胞的自动化系统 (MSCs，又称多能基质细胞)来源于脂肪组织，用于治疗许多严重的 疾病，包括心肌梗塞、移植物抗宿主病和各种自身免疫性疾病 疾病。到目前为止，已有800多项临床试验证实了该疗法的可行性、安全性，在某些情况下， 骨髓间充质干细胞疗法治疗这些疾病的疗效。然而，结果是不确定的，因为(1) 缺乏可靠和优化的MSC制备方案，以及(2)治疗潜力的丧失。 骨髓间充质干细胞经广泛培养扩增。基于其正在申请专利的技术，CG Science Inc. 开发一种自动化的MSC提取系统，提供高细胞回收率和活力，同时 显著减少工艺差异、时间和成本。该公司已经成功地展示了 在第一阶段，其技术可以在45分钟内从单个脂肪组织中提供约60个−1亿MSCs 标本，足以在不扩大培养的情况下提供治疗剂量的MSCs。这个结果 表示与竞争产品相比，MSC的产量提高了约10倍(由于单元中的约4.2倍 恢复和~2.5倍的MSC功能)，并打开了将未培养的原代MSCs用作 高效替代常规培养扩增的MSCs。如果没有文化的扩张，它就会变成 有可能在不到1小时的时间内产生足够的治疗量MSCs(而不是4-6 周)，并在同一天自动给药。自动化系统 具有独特的配置以(1)实现高效的酶消化，(2)集成多个MSC 封闭系统格式的提取步骤，(3)完全自动化MSC提取过程，以及(4) 克服传统的酶法细胞提取的局限性。利用这项技术，高质量的MSCs 可快速、安全、可重复地按临床相关数量生产。在第二阶段， 公司将(1)开发最终产品原型，以确定制造细节并进一步优化 MSC恢复性能，(2)描述新系统的特征并准备数据供FDA提交，以及 (3)展示新系统的临床前成效及卓越表现。 相互竞争的产品。研究团队包括医疗器械专家、干细胞生物学家、 成功合作的工程师和医生。这一项目将导致 实现一种有可能使MSC疗法高度有效和 适用于治疗许多危及生命和难以治疗的疾病。

Project Summary/Abstract This Phase II project aims to develop an automated system for extracting mesenchymal stem cells (MSCs, also known as multipotent stromal cells) from adipose tissues for treating many serious diseases, including myocardial infarction, graft-versus-host disease, and a variety of autoimmune diseases. Over 800 clinical trials to date have established the feasibility, safety, and in some cases efficacy of MSC therapies to treat these diseases. However, the results are inconclusive due to (1) the lack of reliable and optimized MSC preparation protocols, and (2) the loss of therapeutic potential as MSCs are extensively culture expanded. Based on its patent-pending technology, CG Scientific Inc. is developing an automated MSC-extraction system that provides high cell recovery and viability, while significantly reducing process variations, time, and costs. The company has successfully demonstrated in Phase I that its technology can deliver about 60−100 million MSCs in 45 minutes from a single adipose specimen, sufficient to provide a therapeutic dose of MSCs without culture expansion. This result represents a ~10x improvement in MSC output yield over competing products (due to ~4.2x in cell recovery and ~2.5x in MSC function) and opens the opportunity to use un-cultured primary MSCs as a high potency substitute for conventional culture-expanded MSCs. Without culture expansion, it becomes possible to produce sufficient therapeutic amounts of MSCs in less than 1 hour (as opposed to 4-6 weeks conventionally) and administer the MSCs autologously in the same day. The automated system has a unique configuration to (1) enable efficient enzyme digestion, (2) integrate multiple MSC extraction steps in a closed-system format, (3) fully automate the MSC extraction process, and (4) overcome conventional limitations of enzymatic cell extraction. Using the technology, high quality MSCs can be produced in clinically relevant quantities quickly, safely, and reproducibly. In Phase II, the company will (1) develop a final product prototype to work out manufacturing details and further optimize MSC recovery performance, (2) characterize the new system and prepare data for FDA submission, and (3) demonstrate the pre-clinical efficacy and the superior performance of the new system against competing products. The investigator team includes medical device experts, stem cell biologists, engineers and medical doctors who have worked together successfully. This project will result in the realization of an essential tool that has the potential to make MSC therapies highly effective and practical for treating many life-threatening and hard-to-treat diseases.